CTLA4 x IL2RA

Preliminary results show durable anti-tumor activity in multiple solid tumor types among heavily pre-treated patients, including patients whose tumors have progressed through checkpoint inhibitors The results confirm the ability of AU-007, a human IgG1 monoclonal antibody designed using artificial intelligence, to harness the power of interleukin-2 (IL-2) to reduce solid tumors, and support ongoing and planned Phase 2 expansion cohorts in combination with low-dose aldesleukin in melanoma, renal cell carcinoma and non-small cell lung cancer LARKSPUR, Calif.--(BUSINESS WIRE)-- Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, today shared interim results from its Phase 1/2 trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. The data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, Illinois. “The level and scope of anti-tumor activity we’re seeing across solid tumor types are remarkable so early in clinical development, particularly the partial responses and metabolic complete response. The durability of the tumor reductions seen in several patients suggests the formation of immune memory of the cancerous cells. These results validate our long-held belief that AU-007 could widen the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T and natural killer cells that can kill tumor cells and away from immunosuppressive regulatory T cells and the vasculature,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “While other developmental IL-2 therapies focus on changing IL-2 itself, AU-007 is a human antibody that is a well-established therapeutic modality. This provides sources of advantage and differentiation. As we treat patients in earlier lines of therapy, we are confident AU-007 is emerging as a potential best-in-class regimen.” Key findings from the updated results of the AU-007 Phase 1/ 2 study, with data available on 59 patients as of the data cutoff date of April 9, 2024, are as follows. Well-tolerated safety profile: No evidence of vascular leak syndrome or pulmonary edema reported at all dose levels evaluated. All drug-related adverse events were Grade 1 or 2 except for: One patient with Grade 4 CRS that resolved quickly with steroids. This patient was noted retrospectively to have subclinical elevated IL-6 serum levels at baseline. Five patients experienced transient (3-7 days) Grade 3 or 4 lymphopenias that were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue. One patient with Grade 3 anemia who entered the study with Grade 2 anemia. Profound and durable tumor shrinkage observed in multiple tumor types: A patient with large-volume metastatic melanoma whose tumors had progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low dose of IL-2 and experienced 76% shrinkage (unconfirmed partial response) in target lesions at 8 weeks. Another patient with metastatic melanoma whose tumors had also progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of IL-2 and achieved 48% shrinkage in target lesions. A patient with head and neck cancer whose tumors had progressed through an anti-PD-1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced 32% shrinkage (confirmed partial response) in a cervical bone metastasis, as well as reduced pain and improved motor function in an affected hand. A patient with bladder cancer whose tumors had progressed through an anti-PD-L1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable metabolic complete response. Additional tumor shrinkages were observed in patients with widespread large-volume disease in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal cancer. Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles in the IL-2 class: Decreases in peripheral regulatory T cells (Tregs) and increases in CD8/Treg ratios demonstrate AU-007’s ability to redirect IL-2 and prevent the negative feedback loop to Tregs. AU-007 and low-dose aldesleukin also substantially increases peripheral natural killer (NK) cells. AU-007 PK demonstrates dose-proportionality over the dose range tested and no signs of neutralizing anti-drug antibodies (ADAs) activity, and a half life of 15+ days. The Phase 2 expansion cohorts of the AU-007 study are continuing to enroll patients with a focus on melanoma and RCC. The company anticipates presenting updated clinical data in the second half of 2024. Additional Phase 2 expansion cohorts are planned to evaluate AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and without the PD-L1 antibody avelumab. The poster, “Updated results of a phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors,” (Abstract 2527) is available to meeting registrants as an electronic poster on the ASCO online meeting platform and will be presented live in the poster session “Developmental Therapeutics—Immunotherapy” on Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT. To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit . For patients and health professionals in Australia, please visit . About AU-007 AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally designed human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit , X (@AulosBioscience) and LinkedIn.

Preliminary evidence of anti-tumor activity observed in heavily pre-treated patients, including those whose tumors progressed through checkpoint inhibitors Further development of AU-007 to continue in combination with low-dose aldesleukin, with Phase 2 expansion cohorts planned in melanoma, renal cell carcinoma and non-small cell lung cancer LARKSPUR, Calif.--(BUSINESS WIRE)-- Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, today shared new data from its Phase 1/2 clinical trial of AU-007 at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting in San Diego, California. The data, from Phase 1 dose escalation cohorts, continue to indicate that AU-007 is well tolerated as a monotherapy treatment or in a combination therapy regimen with low-dose, subcutaneous aldesleukin (recombinant human IL-2). The data also demonstrate early evidence of anti-tumor activity in patients with several solid tumor cancer types. “These encouraging new data support AU-007’s distinct advantages in the IL-2 class,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “AU-007 continues to be well tolerated by patients, with no pulmonary or generalized edema, no vasculature leakage, and no dose-limiting toxicity to date. We are particularly encouraged by the initial signs of clinical efficacy that have been seen even during dose escalation, which show that heavily pre-treated patients are benefiting from a treatment regimen of AU-007 dosed in combination with low doses of aldesleukin. At this point, we are observing the greatest anti-tumor activity in patients with tumors known to be sensitive to immune-modulating drugs. Tumor shrinkage has been observed in patients with melanoma, bladder, kidney and lung cancers. These data support our decision to focus our Phase 2 expansion cohorts in melanoma, renal cell carcinoma and non-small cell lung cancer. We look forward to presenting clinical data from the Phase 2 expansion cohorts next year.” Created by Biolojic Design, AU-007 is the first human IgG1 monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. Unique among interleukin-2 (IL-2) therapeutics in development, the antibody’s computational design allows it to bind precisely to the portion of IL-2 that binds to CD25. Consequently, AU-007 prevents IL-2 from binding to high-affinity IL-2 receptors on regulatory T cells (Tregs), vasculature, pulmonary tissue and eosinophils, and redirects IL-2 to medium-affinity receptors on effector T cells (Teffs) and natural killer (NK) cells. This novel mechanism of action allows Teffs and NK cells to expand and kill tumor cells. The Phase 1 data presented at SITC is based on 42 patients who received study treatment as of October 13, 2023. AU-007 alone or in combination with aldesleukin was generally well tolerated as administered in the following cohorts: Arm 1A as a monotherapy treatment up to 12 mg/kg Arm 1B with 4.5 mg/kg of AU-007 and escalating aldesleukin (up to 270K IU/kg) given only once on Day 1 Arm 1C with 4.5 mg/kg of AU-007 in combination with aldesleukin (up to 135K IU/kg) also given every two weeks All drug-related adverse events were Grade 1 or 2, with the exception of three transient Grade 3 or 4 lymphopenias that were not associated with adverse outcomes in patients receiving AU-007 and aldesleukin. Transient lymphopenia is a known effect of IL-2 treatment. No patients were discontinued for a drug-related adverse event and no dose-limiting toxicities were observed. Additionally, preliminary evidence of anti-tumor activity was observed in heavily pre-treated patients, including in patients with melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors. Of note, CT scans of a patient with melanoma, who had progressed on anti-CTLA-4 and anti-PD-1 therapy without a response, show a 40% decrease in target tumor lesions, with shrinkage beginning at eight weeks and shrinking further at weeks 16 and 24. The patient continues on the study. Scans of a second patient with RCC, whose tumors had progressed through prior anti-PD-1 therapy, show 20% shrinkage in target tumor lesions beginning at eight weeks, and the patient continues on the study. Across the Phase 1 dose escalation cohorts, nine of 33 (27%) tumor evaluable patients had a best response of stable disease, and 16 patients continue treatment as of the data cutoff date. As previously reported in October, new pharmacodynamic data from the Phase 1 dose escalation study show favorable trends toward decreasing Tregs with concordant increases in the CD8 Teff:Treg ratio, initial interferon-gamma increases, and absolute eosinophil decreases. These findings are consistent with the novel mechanism of action of AU-007 redirecting IL-2 away from the cells that express high-affinity IL-2 receptors that contain CD25, which include Tregs, vascular endothelial cells and eosinophils, and toward CD8 Teff cells and NK cells that can elicit anti-tumor immune effects. The Phase 1/2 clinical trial of AU-007 is a two-part, open label, first-in-human study evaluating the safety, tolerability, immunogenicity and clinical activity of AU-007 in patients with unresectable locally advanced or metastatic cancer. The trial is currently enrolling patients at multiple locations in the United States and Australia. The company anticipates transitioning to the Phase 2 portion of the AU-007 study by late 2023 or early 2024, with Phase 2 dose expansion cohorts planned in melanoma, RCC and NSCLC. The poster presentation is available on the Aulos Bioscience website in the Abstracts and Publications section. To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit . For patients and health professionals in Australia, please visit . About AU-007 AU-007 is a computationally designed, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally designed human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit , X (Twitter) at @AulosBioscience and LinkedIn.

Phase 1/2 ABILITY study advancing to sixth dose escalation cohort following positive review of safety and pharmacodynamic data from fifth cohort Initial PK/PD data from ABILITY’s fifth dose escalation cohort expected alongside updated anti-tumor data in calendar Q1 2023 $36.2 million in cash and cash equivalents at December 31, 2022 provides expected runway through the completion of the ABILITY study and through calendar Q2 2024 Management hosting conference call and webcast today at 8:30 am ET TORONTO and HOUSTON, Feb. 07, 2023 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or “the Company”) (NASDAQ: MDNA TSX: MDNA), a clinical stage immunotherapy company, today announced its financial results and operational highlights for the quarter ended December 31, 2022, and that the Phase 1/2 ABILITY study of MDNA11 has advanced to a sixth dose escalation cohort. All dollar amounts are in Canadian currency unless otherwise noted. “Encouraged with MDNA11’s tolerability pro end-stage cancer patients together with its enduring trend demonstrating dose-dependent expansion of lymphocytes, we are pleased to advance the ABILITY study to the sixth dose escalation cohort,” said Dr. Fahar Merchant, President and CEO of Medicenna. “MDNA11 has thus far functioned as intended, by displaying durable tumor control with better tolerability upon repeat dosing, showing dose-dependent increase in exposure without immunogenicity, and boosting anti-cancer immune cell expansion without pro-tumoral immune suppression. With these attributes together with early signs of anti-tumor activity, we hope to bolster MDNA11’s efficacy in a select group of less advanced cancer patients at the optimum dose in ABILITY’s upcoming Phase 2 monotherapy dose expansion cohort.” Program highlights for the quarter ended December 31, 2022, along with recent developments include: MDNA11: IL-2 Superkine Program Enrollment is complete in the fifth dose escalation cohort of the Phase 1/2 ABILITY study of MDNA11, with no dose-limiting toxicities, dose interruptions, dose de-escalations, or treatment discontinuations due to safety issues observed to date. Preliminary pharmacodynamic (PD) data showed enhanced stimulation of lymphocyte expansion relative to baseline in the fifth cohort compared to all prior dose escalation cohorts, demonstrating MDNA11’s ability to boost immune activity may be enhanced at higher doses. Based on these findings, the trial has advanced to a sixth dose escalation cohort. Participants in the sixth dose escalation cohort will receive 30, 60, and 90 µg/kg “priming” doses of MDNA11 followed by a further step-up to a fixed 120 µg/kg dose. MDNA11 is dosed intravenously every two weeks in the ABILITY study. In November 2022, Medicenna presented safety, pharmacokinetic (PK), and PD data from the first four (low and mid) dose escalation cohorts of the ABILITY study at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting. Safety data indicated that MDNA11 was well tolerated with no dose limiting toxicities observed. PK data showed dose-dependent increases in exposure that were sustained with repeat dosing, suggesting there is no clinically meaningful anti-drug-antibody response to MDNA11. PD data showed dose-dependent stimulation of anti-cancer immunity, with MDNA11 preferentially stimulating the proliferation and expansion of anti-cancer CD8+ T and NK cells but not Tregs (associated with pro-tumor immune pathways) or eosinophils (associated with vascular leak syndrome, a known side effect of the only approved IL-2 therapy). The results presented at the SITC meeting provide mechanistic support for previously reported anti-tumor activity data demonstrating MDNA11’s single-agent potential in advanced solid tumors unresponsive to established treatments. These data show that five of fourteen (36%) evaluable patients in the ABILITY study’s first four dose escalation cohorts achieved tumor control (partial response or stable disease), including one fourth-line metastatic pancreatic cancer patient who achieved a confirmed partial response. In December 2022, previously reported data from the Phase 1/2 ABILITY study of MDNA11 were featured in an oral presentation at the 2022 Immunotherapy Bridge Conference. The presentation, titled “Early Results of an IL-2 Superkine (MDNA11) from the Phase 1/2 ABILITY Study in Advanced Solid Tumors” was delivered by Arash Yavari, M.B.B.S., DPhil., M.R.C.P., Principal Investigator at the Radcliffe Department of Medicine, University of Oxford and Principal Clinical Advisor to Medicenna. Bizaxofusp (formerly MDNA55): Empowered IL-4 Superkine Program In January 2023, the full results of a single-arm Phase 2b trial of bizaxofusp (formerly MDNA55) in patients with recurrent glioblastoma were published in the peer-reviewed journal Neuro-Oncology. Results showed that the trial met its primary endpoint, with median overall survival (mOS) in the primary and supportive analysis populations exceeding the trial’s pre-defined success criteria. Medicenna continues to pursue potential partnership opportunities to facilitate bizaxofusp’s further development and, if approved, commercialization. Intellectual Property In January 2023, the U.S. Patent and Trademark Office issued U.S. Patent No. 11,542,312. The patent provides intellectual property protection for methods of treating cancer with an IL-2 Superkine and PD1/PDL1 or CTLA-4 checkpoint inhibitor, administered in combination or as a single agent BiSKIT™. The patent’s term extends into at least 2039 without accounting for any potential extensions. Expected Upcoming Milestones Initial PK/PD data from the ABILITY study’s fifth dose escalation cohort and updated anti-tumor activity data from the first four dose escalation cohorts are expected in calendar Q1 2023. Early anti-tumor activity data from the ABILITY study’s sixth dose escalation cohort and single agent expansion phase (Phase 2) are expected in calendar Q3 2023. Early anti-tumor activity data from the ABILITY study’s combination arm are expected in calendar Q4 2023. Financial Results Medicenna had cash and cash equivalents of $36.2 million at December 31, 2022. These funds are expected to provide the Company with sufficient capital to execute its current planned expenditures through the completion of the ABILITY study and through calendar Q2 2024 based on its current plans and projections. Net loss for the quarter ended December 31, 2022, was $1.1 million, or ($0.02) per share, compared to a net loss of $4.8 million or ($0.09) per share for the quarter ended December 31, 2021. The decrease in net loss for the quarter ended December 31, 2022, compared with the quarter ended December 31, 2021, was primarily a result of a non-cash gain of $3.7 million related to the change in valuation of a non-cash warrant liability associated with the August 2022 financing. Research and development expenses of $2.9 million were incurred during the quarter ended December 31, 2022, compared with $2.9 million incurred in the quarter ended December 31, 2021. Research and development expenses were consistent quarter over quarter. General and administrative expenses of $2.0 million were incurred during the quarter ended December 31, 2022, compared with $2.0 million during the quarter ended December 31, 2021. General and administrative expenses were consistent quarter over quarter. Medicenna’s condensed consolidated interim financial statements for the quarter ended December 31, 2022 and the related management’s discussion and analysis (MD&A) will be available on SEDAR at and EDGAR at . Conference Call and Webcast Medicenna will host a conference call and webcast today at 8:30 am ET. To access the call please dial 1-877-407-9716 from the United States or 1-201-493-6779 internationally and refer to conference ID: 13735304. To access the live webcast, visit this link to the event. Following the live webcast, an archived version of the call will be available on Medicenna’s website. About Medicenna Medicenna is a clinical stage immunotherapy company focused on the development of novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior CD122 (IL-2 receptor beta) binding without CD25 (IL-2 receptor alpha) affinity thereby preferentially stimulating cancer killing effector T cells and NK cells. Medicenna’s early-stage BiSKITs™ program, (Bifunctional SuperKine ImmunoTherapies) is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained Fast-Track and Orphan Drug status from the FDA and FDA/EMA, respectively. Forward Looking Statements This news release contains forward-looking statements within the meaning of applicable securities laws that relate to the future operations of the Company, plans and projections and other statements that are not historical facts including, but not limited to, statements related to the clinical potential, safety and tolerability pro development of MDNA11, the clinical potential an development of bizaxofusp (formerly MDNA55) and partnering efforts in connection therewith, intellectual property protection, expected upcoming milestones and cash runway and planned expenditures. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest Annual Information Form and Annual Report on Form 20-F of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada and the United States. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. Further Information For further information about the Company please contact: Elizabeth Williams, Chief Financial Officer, 416-648-5555, ewilliams@medicenna.com Investor Contact For more investor information, please contact: Dan Ferry, Managing Director, LifeSci Advisors, 617-430-7576, daniel@lifesciadvisors.com